Certain drugs are known to produce differential mydriatic effects in the heavily pigmented and lightly pigmented iris. The drugs such as atropine, cyclopentolate, and tropicamide are less effective in heavily pigmented iris. With the aid of radiolabelled atropine uptake, binding and release characteristics of these autonomic drugs will be examined in the pigmented and the non-pigmented rabbit iris. Parallel pharmacologic experiments in two types of irides will also be carried out to study the relevance of drug binding by the tissue to the pharmacologic effect. Pharmacologic experiments in rabbit are complicated not only by the presence of atropinase but also by melanin. Thus the diration of mydriatic (or cycloplegic) effects of atropine will be studied in atropinase positive and negative, albino as well as nonalbino rabbits. The binding of 3H-atropine to light and dark human iris will also be examined. It appears from the preliminary experiments that in heavily pigmented iris, drug is markedly accumulated by the pigment, melanin, or melanin-containing structures. Hence, lesser concentration of the drug is available at the pharmacologic receptors. In the other series of experiments, binding characteristics of drugs will be studied on melanosomes. Since many drugs like Chlorpromazine and other psychotropic drugs, antibiotics and chlorquine are accumulated by the pigmented iris an attempt will be made to displace the bound drug by dopamine and related substances. Thus it should be possible to displace toxic drugs by nontoxic drugs. BIBLIOGRAPHIC REFERENCES: Antagonism of morphine-induced mitosis by naloxone and amphetamine in rabbits. M.C. Gerald, M.Y.-W. Chan and P.N. Patil. Pharmacol. Res. Communication, Vol 8, p. 591-599, 1976. Competitive binding between between cocaine and various drugs to synthetic levodopa melanin. R. Baweja, T.D. Sokoloski and P.N. Patil. J. Pharm. Sci. Accepted for publication Jan. 1977.